Trial Outcomes & Findings for Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap (NCT NCT01575756)

NCT ID: NCT01575756

Last Updated: 2018-03-09

Results Overview

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The mean ratio of normalized area under the curve was calculated as Octafibrin/FIBRYGA® over Haemocomplettan® P/RiaSTAP(TM)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Results posted on

2018-03-09

Participant Flow

Participant milestones

Participant milestones
Measure
Octafibrin/FIBRYGA® Followed by Haemocomplettan® P/RiaSTAP(TM)
Participants received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once followed by Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once 45 days later.
Haemocomplettan® P/RiaSTAP(TM) Followed by Octafibrin/FIBRYGA®
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once followed by Octafibrin/FIBRYGA® 70 mg/kg BW intravenously once 45 days later.
Treatment Period 1
STARTED
11
11
Treatment Period 1
COMPLETED
11
11
Treatment Period 1
NOT COMPLETED
0
0
Treatment Period 2
STARTED
11
11
Treatment Period 2
COMPLETED
11
11
Treatment Period 2
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Full Analysis Set
n=22 Participants
All randomised participants who received at least 1 infusion of study medication (Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)) and for whom any post-treatment data were available.
Age, Continuous
26.0 Years
STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male
Female
15 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The mean ratio of normalized area under the curve was calculated as Octafibrin/FIBRYGA® over Haemocomplettan® P/RiaSTAP(TM)

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Ratio of Octafibrin/FIBRYGA® to Haemocomplettan® P/RiaSTAP(TM) for Fibrinogen Activity Normalized Area Under the Curve Unstandardized
1.196 ratio
Interval 1.117 to 1.281

PRIMARY outcome

Timeframe: 1 hour post-treatment

Population: Full analysis set: All randomised participants who received at least 1 infusion of study medication (Octafibrin/FIBRYGA®) and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)) and for whom any post-treatment data were available.

Thromboelastometry (ROTEM®) was used to measure maximum clot firmness. Thromboelastometry is a method for the continuous measurement of clot formation. Maximum clot firmness is a functional parameter that depends on the activation of coagulation, the platelet and fibrinogen content of the blood sample, and the polymerisation and cross-linking of the fibrin network. In order to obtain comparable results from all study centres, maximum clot firmness data were assessed from frozen citrated plasma samples in a central laboratory. As these samples did not contain platelets that would be found in the whole blood assay, the fibrinogen content primarily defined the maximum clot firmness.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=22 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=22 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Comparison of Maximum Clot Firmness Between Octafibrin/FIBRYGA® and Haemocomplettan® P/RiaSTAP(TM) at 1 hr Post Infusion
9.68 mm
Interval 8.37 to 10.99
10.00 mm
Interval 8.07 to 11.93

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Fibrinogen Activity Normalized Area Under the Curve Unstandardized
1.62 h•kg•g/L/mg
Standard Deviation 0.45
1.38 h•kg•g/L/mg
Standard Deviation 0.47

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses; had any post-T data; did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The normalized area under the curve was standardized to a dose of 70 mg/kg.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Fibrinogen Activity Normalized Area Under the Curve Standardized
113.70 g•h/L
Standard Deviation 31.54
96.39 g•h/L
Standard Deviation 32.89

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Maximum Plasma Concentration Normalized (Cmaxnorm)
0.018 kg•g/L/mg
Standard Deviation 0.005
0.018 kg•g/L/mg
Standard Deviation 0.005

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Maximum Plasma Concentration (Cmax) Unstandardized
1.390 g/L
Standard Deviation 0.369
1.265 g/L
Standard Deviation 0.309

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses; had any post-T data; did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment. The maximum plasma concentration was standardized to a dose of 70 mg/kg.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Maximum Plasma Concentration (Cmax) Standardized
1.266 g•h/L
Standard Deviation 0.338
1.271 g•h/L
Standard Deviation 0.312

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Incremental in vivo recovery was calculated as the maximum increase in plasma fibrinogen (fibrinogen activity assay data) within 4 hours post-treatment as compared with pre-treatment (expressed as an absolute mg/dL concentration in plasma), divided by the exact dose of Octafibrin/FIBRYGA® or Haemocomplettan® P/RiaSTAP(TM) (expressed as mg/kg dosed).

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Incremental in Vivo Recovery
1.787 mg/dL/(mg/kg)
Standard Deviation 0.458
1.770 mg/dL/(mg/kg)
Standard Deviation 0.442

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Classical in vivo recovery was calculated as: 100 x the maximum increase in plasma fibrinogen (fibrinogen activity assay data) within 4 hours post-treatment as compared with pre-treatment (expressed as an absolute mg/dL concentration in plasma) x the plasma volume (mL), divided by the exact dose of Octafibrin/FIBRYGA® or Haemocomplettan® P/RiaSTAP(TM) (expressed as mg).

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Classical in Vivo Recovery
64.397 percentage
Standard Deviation 11.519
66.046 percentage
Standard Deviation 11.635

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Time to Reach Maximum Plasma Concentration (Tmax)
2.148 h
Standard Deviation 1.475
1.417 h
Standard Deviation 2.054

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Terminal Half-life (t½)
75.940 h
Standard Deviation 23.831
69.378 h
Standard Deviation 16.006

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Mean Residence Time (MRT)
106.272 h
Standard Deviation 30.927
98.977 h
Standard Deviation 20.812

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Clearance
0.665 mL/h/kg
Standard Deviation 0.197
0.804 mL/h/kg
Standard Deviation 0.255

SECONDARY outcome

Timeframe: Baseline to 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment

Population: Pharmacokinetic (PK)-per protocol dataset: All randomised participants who received ≥ 90% of the treatment (T) doses, had any post-T data, did not receive any fibrinogen (F) containing blood products between T and 14 days post-T in both study periods; had sufficient PK data for analysis; had a ≥ 50 mg/dL increase in plasma F within 4 hours post-T.

Fibrinogen activity was determined via a validated Clauss assay (fibrinogen activity) and fibrinogen-specific enzyme-linked immunosorbent assay (ie, fibrinogen antigen) using paired antibodies for fibrinogen antigen. All determinations were performed on frozen plasma samples in a central laboratory. The Clauss assay was modified and validated to achieve a limit of quantification of 0.2 g/L. The pharmacokinetic analysis was assessed individually using a non-compartmental model. Plasma levels were measured at Baseline, and at 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216, and 312 hours post-treatment.

Outcome measures

Outcome measures
Measure
Pharmacokinetic (PK)-Per Protocol Dataset
n=21 Participants
Ratio comparison of participants who received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once, and participants who received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once
Haemocomplettan® P/RiaSTAP(TM)
n=21 Participants
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Volume of Distribution at Steady State (Vss)
70.158 mL/kg
Standard Deviation 29.860
76.631 mL/kg
Standard Deviation 19.579

Adverse Events

Octafibrin/FIBRYGA®

Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths

Haemocomplettan® P/RiaSTAP(TM)

Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Octafibrin/FIBRYGA®
n=22 participants at risk
Participants received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once.
Haemocomplettan® P/RiaSTAP(TM)
n=22 participants at risk
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Gastrointestinal disorders
Abdominal pain
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Reproductive system and breast disorders
Vaginal haemorrhage
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).

Other adverse events

Other adverse events
Measure
Octafibrin/FIBRYGA®
n=22 participants at risk
Participants received Octafibrin/FIBRYGA® 70 mg/kg body weight (BW) intravenously once.
Haemocomplettan® P/RiaSTAP(TM)
n=22 participants at risk
Participants received Haemocomplettan® P/RiaSTAP(TM) 70 mg/kg BW intravenously once.
Ear and labyrinth disorders
Vertigo
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Diarrhoea
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Dyspepsia
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Food poisoning
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Gingival bleeding
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Haematemesis
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Gastrointestinal disorders
Nausea
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
General disorders
Asthenia
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
General disorders
Fatigue
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
General disorders
Pain
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
General disorders
Pyrexia
9.1%
2/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
13.6%
3/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Immune system disorders
Mild allergic skin reaction
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Infections and infestations
Nasopharyngitis
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
9.1%
2/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Infections and infestations
Upper respiratory tract infection
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Infections and infestations
Urinary tract infection
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Injury, poisoning and procedural complications
Animal bite
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Injury, poisoning and procedural complications
Contusion
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Injury, poisoning and procedural complications
Fall
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Injury, poisoning and procedural complications
Post procedural haemorrhage
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Injury, poisoning and procedural complications
Traumatic haematoma
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Investigations
Alanine aminotransferase increased
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Investigations
Aspartate aminotransferase increased
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Investigations
Haemoglobin decreased
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Metabolism and nutrition disorders
Decreased appetite
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Metabolism and nutrition disorders
Iron deficiency
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Arthralgia
9.1%
2/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Flank pain
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Haemarthrosis
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Joint swelling
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Musculoskeletal and connective tissue disorders
Pain in extremity
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
9.1%
2/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Nervous system disorders
Dizziness
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Nervous system disorders
Headache
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
9.1%
2/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
Vascular disorders
Haematoma
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).
4.5%
1/22
Safety analysis dataset: All randomised participants who received at least 1 infusion of study medication (any part of an infusion of Octafibrin/FIBRYGA® and/or any part of an infusion of Haemocomplettan® P/RiaSTAP(TM)).

Additional Information

Director of Clinical Operations

Octapharma USA

Phone: 201 604-1149

Results disclosure agreements

  • Principal investigator is a sponsor employee Octapharma agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Octapharma supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. Octapharma also reserves the right to review data prior to publishing and provide comments/changes within a certain time period.
  • Publication restrictions are in place

Restriction type: OTHER